The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks

被引:281
作者
Loizou, JI
El-Khamisy, SF
Zlatanou, A
Moore, DJ
Chan, DW
Qin, J
Sarno, S
Meggio, F
Pinna, LA
Caldecott, KW
机构
[1] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England
[2] Baylor Coll Med, Houston, TX 77030 USA
[3] Univ Padua, I-35121 Padua, Italy
[4] Venetian Inst Mol Med, I-35129 Padua, Italy
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0092-8674(04)00206-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CK2 was the first protein kinase identified and is required for the proliferation and survival of mammalian cells. Here, we have identified an unanticipated role for CK2. We show that this essential protein kinase phosphorylates the scaffold protein XRCC1 and thereby enables the assembly and activity of DNA single-strand break repair protein complexes in vitro and at sites of chromosomal breakage. Moreover, we show that inhibiting XRCC1 phosphorylation by mutation of the CK2 phosphorylation sites or preventing CK2 activity using a highly specific inhibitor ablates the rapid repair of cellular DNA single-strand breaks by XRCC1. These data identify a direct role for CK2 in the repair of chromosomal DNA strand breaks and in maintaining genetic integrity.
引用
收藏
页码:17 / 28
页数:12
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